Quantifying the association between psychological distress and low back pain in urban Europe: a secondary analysis of a large cross-sectional study

Objectives This study aims to estimate the prevalence of low back pain (LBP) in Europe and to quantify its associated mental and physical health burdens among adults in European urban areas. Design This research is a secondary analysis of data from a large multicountry population survey. Setting The population survey on which this analysis is based was conducted in 32 European urban areas across 11 countries. Participants The dataset for this study was collected during the European Urban Health Indicators System 2 survey. There were a total of 19 441 adult respondents but data from 18 028, 50.2% female (9 050) and 49.8% male (8 978), were included in these analyses. Primary and secondary outcome measures Being a survey, data on the exposure (LBP) and outcomes were collected simultaneously. The primary outcomes for this study are psychological distress and poor physical health. Results The overall European prevalence of LBP was 44.6% (43.9–45.3) widely ranging from 33.4% in Norway to 67.7% in Lithuania. After accounting for sex, age, socioeconomic status and formal education, adults in urban Europe suffering LBP had higher odds of psychological distress aOR 1.44 (1.32–1.58) and poor self-rated health aOR 3.54 (3.31–3.80). These associations varied widely between participating countries and cities. Conclusion Prevalence of LBP, and its associations with poor physical and mental health, varies across European urban areas.

score of >=4 is a standard cutpoint, please provide references. Results: Table A, supplementary, it would be easier to read if it were sorted by most to least percentages with LBP. Could you also add a column with the county of each urban area for those not familiar? The results of the prevalence of LBP stratified by age category are discussed in the text of the results but not presented in a table. I think such a table would be interesting to add if space allows, especially with the large differences between countries. For Table 1.0, please indicate in the table title that the ORs are unadjusted. It's interesting that those with primary or secondary education had higher prevalences of low back pain than those with no formal education. In the Discussion section, I would be interested in the authors' speculation about why this might be. On page 11, lines 50-52, after adjustment, only mild attenuation was noticed, not effect modification. For Figure 2.0, does the horizontal line represent an OR of 1.0? This should be labeled on the figure. Same with figure 3. Discussion: This does a good job of summarizing the study's findings and putting them in the context of other research. The authors are careful not to state any associations of cause and effect, which is appropriate for these cross-sectional data. However, a limitations paragraph is needed in this section, with the foremost limitation being that these data were collected at the same time and therefore cause and effect cannot be determined (but future studies should examine this in more detail!).
Page 5 Line 27: Can you clarify the wording here. It is not clear how you assessed the higher mental health burden? Do you mean that mental health has a higher association with low back pain in coutries with a smaller prevelance of low back pain?
INTRODUCTION: Page 6 Line 20: I'm not sire the word disappointing is appropriate. It would indicate that there is no improvement at all. Could this be termed "improvements in outcomes may be modest at best".

METHODS:
Page 8 Line 6: Were that any questions about the severity, chronicity etc of symptoms. For example, those with more severe/chronic LBP may have more seveve PD etc than those without. If not then this could be a potential limitation of the study.
Page 8 Line 39: For the reader I think again, it would be worthwhile clarifying which were the exposure and outcome variables.
Page 8 Line 40: For the multivariate logistic regression, can you confirm if this included both self-rated health and PD predictor variables? Of not, then this would be worth running and presenting to see if there is an effect of accounting for each predictor.

RESULTS:
Page 10 Line 16: The wording statistically signficantly hard to follow. I was suggest just using the word "signficantly" as this implies the results was based off statistical results.
Page 11 Line 27: Please check the wording of "risk" throughout the results/manuscript given odds ratio are presented and not risk ratios.
Page 12 Line 11: For both of these tables can you please make it clearer that the 1.0 OR is the reference group in the model. Individuals may read this and assume there is not an effect of that variable. This could be done with 1.0 (Ref) or just state Ref in that box.

DISCUSSION:
Page 16 Line 23: Can you discuss what the results of the American study mean in the context of your study? Given the looks at PD as the outcome compared to you looking at back pain as the outcome. Particularly in the following sentence you state that then PD predicts back pain chronicity (outcome). Could there then be a bidirectional relationship between PD and back pain. Even though your research is cross-sectional I believe this can be discussed here for the reader.
Page 16 Line 38: Again I don't follow what you mean by a greater burder of associated mental health effects? Do you mean, areas with a low prevelance of low back pain, tend to have a greater association between PD and back pain?
Page 17 Line 31: Please add a strengths and limitations paragraph to the manuscript. For example, cross-sectional and self-report nature of LBP would be limitations.

FIGURES:
Page 24: Given you present adjusted ORs, please restate what the models were adjusted for in the figure note for ease for readers.

REVIEWER
Underwood, Martin Warwick University, Warwick Medical School REVIEW RETURNED 15-Jan-2021

GENERAL COMMENTS
This paper adds to our knowledge on the prevalence of back pain. It does however not help our understanding of back pain and back pain disability. It is simply creating more 'why' questions. Clearly beyond scope of this paper but understanding if you ask the same question to people in Norway and Lithuania twice as many answer 'yes' in Lithuania, is really important. Is it something in the translation, the question having developed in English only, or is it a culturally driven difference in the interpretation of the question, or is there a real difference in prevalence? The authors may wish to comment on whether there may be reasons for their observations other than differences in prevalence. It might be interesting to see if global burden of disease data shows similar differences to shed some light on why this might. I have no fundamental concerns about the conduct of the study. It would , however, be nice to know if there was a pre-specified statistical analysis plan that could be included as supplementary material Whilst the overall observations on the associations between socioeconomic, psychological variable, and poor self-rated health and back pain are robust, but they are not novel findings. I would be inclined to give them less prominence for this reason. The differences in strength of these associations by nation is novel and of interestthis could be explored more in the discussion. More could be said about how these differences might be explain differences in overall prevalencewhy should there be no association between psychological distress in Norway and an odds ratio of around two for this in Lithuania? More up to date references are available for prevalence of, and disability caused by, low back pain. Notably, reference 36 (Volinn) is out of date. It is now generally believed prevalence of low back pain is high in both developed and less developed nations. See for example a fairly recent systematic review of back pain prevalence studies from Africa https://pubmed.ncbi.nlm.nih.gov/30037323/. I would prefer less use of non-standard abbreviations. Specifically, PD for psychological distress. I kept needing to remind myself I was not reading a Parkinson's disease study. Also why say UA instead of urban area. I am not convinced that the approach of reporting individual country prevalences when compared to the European average is robust. I may be misunderstanding, but presumably the European data will include the all the individual country data. More detail on this analysis is needed and revie by a statistical expert. Although, I think the data stand as they are without any need for any statistical gloss.
Whilst it is possible to work out what the figures mean they could be made easier to understand with properly labelled Y axes and actual values attached to bars in all four figures. General comments: This is an interesting analysis with many strengths, the most notable being the large sample size with a widespread geographic population. The variance in prevalence rates of low back pain by geographic areas is very interesting, as is the finding that psychological distress was strongly associated with prevalence of low back pain even in countries with relatively low prevalences of LBP. I have only minor issues with the methodology, described below.

VERSION 1 -AUTHOR RESPONSE
Comments noted and appreciated.

Abstract
If possible, it would be easier to understand the results if the referent groups were also specified where they are unclear. For example, people with primary education were at 2.28 times the odds of back pain compared to whom?
These comments are noted. Given the strict word count for the abstract section, it may not be feasible to provide further explanation of the comparator categories in the abstract.
The sentence has been rephrased to read: The overall European Prevalence of low back pain was 44.6% (43.9-45.3) widely ranging from 33.4% in Norway to 67.7% in Lithuania. After accounting for sex, age, socio-economic status, and formal education, adults in urban Europe suffering low back pain had higher odds of psychological distress aOR 1.44 (1.32-1.58) and poor self-rated health aOR 3.54 (3.31-3.80). These associations varied widely between participating countries and cities.
See page 2 lines 19 -20, page 3 lines 1 -3 Introduction: This makes a good case for the enormous burden of back pain and the benefits that this analysis brings (uniform data gathered in many different geographic areas). The sentences in the last paragraph about studying back pain among urban and rural populations were less convincing and led me to expect comparisons between urban and rural populations, which your study wasn't really designed to do.
This has been modified. The sentences in the last paragraph of the introduction now read thus: In addition, although LBP affects all population settings, the burden is expected to differ in urban settings.
See page 5 lines 6 -7 What study question were your analyses attempting to address and what hypothesis did you have about LBP and PD in urban populations among your study participants?
The study question has been included in the introduction section and reads as follows: Amongst adults dwelling in urban Europe, what is the risk of psychological distress in those with low back pain compared to those without low back pain.

Exposure: low back pain
Comparator: those without low back pain

Outcome: psychological distress
Null Hypothesis: there is no significant difference in the risk of psychological distress among adults in urban Europe who suffer low back pain compared to those who do not.

Methods:
The descriptions of the EURO-URHIS 2 data and each of the independent variables are very clear. The statistical analysis section is also very clear.
I inferred from the abstract that PD and general health are the outcome variables that are predicted by the presence or absence of back pain (rather than back pain being predicted by PD and general health), but please also state this explicitly in the Methods since the crosssectional nature of these data make that unclear.
Comments noted.
The exposure and outcome variables have been stated explicitly in the methods section.
Page 6 line 14 -18 and reads thus: The exposure (predictor) variable for this study was low back pain whilst psychological distress and self-rated health were the main outcome variables. Data was also collected on potential socio-demographic confounders known to have a relationship with the predictor. These include: age, sex, level of formal education attained, and socio-economic status. All these were accounted for through multivariable regression.
Consider not dichotomizing PD and doing linear regression with PD as a continuous outcome variable. You're losing quite a lot of information from the continuous variable by imposing a cutpoint. If a score of >=4 is a standard cutpoint, please provide references.
The relevant reference has been provided.
The Swedish validation study cited aimed to validate the GHQ-12 for the assessment of mental health at population level. They found that the best cut-ff point with excellent discriminant validity was >=4. It's interesting that those with primary or secondary education had higher prevalences of low back pain than those with no formal education. In the Discussion section, I would be interested in the authors' speculation about why this might be.
Comments noted.
The authors have not given prominence to discussions around the sociodemographic factors associated with LBP. They were identified as potential confounders that had to be accounted for through multivariable regression. Hence speculations about the mechanisms of the interesting association of LBP and educational status are not pursued.
On page 11, lines 50-52, after adjustment, only mild attenuation was noticed, not effect modification.
The relevant section has been reworded as recommended.
See page 11 lines 6 -7 For Discussion: This does a good job of summarizing the study's findings and putting them in the context of other research. The authors are careful not to state any associations of cause and effect, which is appropriate Comments noted.
We have included a section on limitations of our study on page 17 lines for these cross-sectional data. However, a limitations paragraph is needed in this section, with the foremost limitation being that these data were collected at the same time and therefore cause and effect cannot be determined (but future studies should examine this in more detail!).

-10 and it reads thus:
The data informing this analysis was generated from a population crosssectional study. As a result, the temporal relationship between exposure and outcomes cannot be established by our research as both information were collected at the same time. Despite rigorous efforts to minimize bias in the EURO URHIS 2 study, such surveys may retain the possibility of information bias on account of recall as well as selection bias from non-response. Additionally, our research is unable to explore if a dose-response relationship exists between LBP and psychological distress. Further research is required to answer these questions. Page 4 Line 19: Suggest a minor change to wording to make then conclusion more succint as widely, differently and vary all insinuate the same thing in this context. "The prevalence of low back pain, and its associations with poor physical and mental health, varies across European urban areas.
Comments noted.
Modifications have been effected. The aim was to communicate a variation in the prevalence of LBP as well as a difference in the variation pattern of its associated psychological distress.
The recommended phrasing has been adopted. See page 3 lines 5 -6 SUMMARY BOX: Page This has been clarified Page 6 lines 14 -18 and reads thus: The key exposure (predictor) variable for this study was low back pain whilst psychological distress and self-rated health were the main outcome variables.
Page 8 Line 40: For the multivariate logistic regression, can you confirm if this included both self-rated health and PD predictor variables? Of not, then this would be worth running and presenting to see if there is an effect of accounting for each predictor.
Comments noted.
We have treated self-rated health and psychological distress as outcome variables and LBP as the predictor/exposure based on existing literature and the theory of biological plausibility.

RESULTS:
Page 10 Line 16: The wording statistically signficantly hard to follow. I was suggest just using the word "signficantly" as this implies the results was based off statistical results.
The wording has been amended as recommended.
Page 11 Line 27: Please check the wording of "risk" throughout the results/manuscript given odds ratio are presented and not risk ratios.
Wordings have been modified as recommended now read 'higher odds' (4) NWPHO (North West Public Health Observatory) Core Questions and Methods. The NWPHO was asked to provide a framework for the conduct of lifestyle surveys across the North West region of England. The questions were further tested against European targets. Following consultation around the region a set of questions has been developed that is recommended as a minimum core that will help to collect data on key lifestyle topics. The questions were chosen for being able to provide data to support target setting and monitoring and if they had been previously validated. A final report was written in 2007 and subsequently the questions were used to conduct a regional lifestyle survey. The age range targeted 16 years and older. Whilst there has been no translation, options for translation have been offered.
At a 3-day steering group meeting the lead from each working group presented a paper detailing the items from their domain that had been deemed appropriate for measuring UHIs within this domain. Through discussion, items identified as being the most appropriate, practical and generic (in terms of being understood in multiple European countries after translation) were identified for inclusion in the Euro-Urhis data collection tool. If a previously validated source could not be found for any UHI necessary for Euro-Urhis 2 suitable questions were drafted by core members of the steering group and management committee. These were then circulated to members of the steering group and to city partners for commentary. material Whilst the overall observations on the associations between socio-economic, psychological variable, and poor selfrated health and back pain are robust, but they are not novel findings. I would be inclined to give them less prominence for this reason.
Comments have been noted.
The section in the abstract and discussion that seemed to give prominence to these have been modified.
See page 2 lines 19 -20, page 3 lines 1 -3 The differences in strength of these associations by nation is novel and of interestthis could be explored more in the discussion. More could be said about how these differences might be explain differences in overall prevalencewhy should there be no association between psychological distress in Norway and an odds ratio of around two for this in Lithuania?
Further discussion has been added to this section.
See Page 16 lines 17 to 20.
More up to date references are available for prevalence of, and disability caused by, low back pain. Notably, reference 36 (Volinn) is out of date. It is now generally believed prevalence of low back pain is high in both developed and less developed nations. See for example a fairly recent systematic review of back pain prevalence studies from Africa https://pubmed.ncbi.nlm.nih.gov/3003732 3/.
Comments noted and appreciated.
New reference suggestion is appreciated and has been included in place of the outdated reference. The corresponding section in the discussion has also been rephrased to reflect the current evidence.
Page 16 Line 7 now reads: Globally, low back pain is quite prevalent in high and low-and-middleincome countries.
I would prefer less use of non-standard abbreviations. Specifically, PD for psychological distress. I kept needing to remind myself I was not reading a Parkinson's disease study. Also why say UA instead of urban area.
Comments noted.
UA and PD abbreviations have now all been written out in full to read Urban areas and psychological distress.
I am not convinced that the approach of reporting individual country prevalences The comments are noted. when compared to the European average is robust. I may be misunderstanding, but presumably the European data will include the all the individual country data. More detail on this analysis is needed and revie by a statistical expert. Although, I think the data stand as they are without any need for any statistical gloss.
We now refer to the 'overall prevalence' rather than 'European average'.

GENERAL COMMENTS
Thanks, the authors have done a commendable job responding to my comments.

GENERAL COMMENTS
I would like to thank the authors for taking the time to respond to my comments in detail. I have now reviewed these and they have been adequately implemeneted. How the exposures and outcomes were treated in the statistical models is now clearer. Outside of the responses, I have some minor comments that should be addressed. I apologise if I missed any of these in the original review.

RESULTS:
Page 10 Line 1: Throughout the results please present the 95% confidence intervals anytime a value from statistical models is reported to allow readers to easily determine the precison of the estimate. EG on line 19 "Whereas those with No formal education had a 44% increase in risk." The 95% CI should be presented with this.
Page 10 Line 10: The wording needs to be updated from 'risk' to 'odds' given the odds ratios were used for consistency. This also needs to be updated in subsequent paragraphs.

DISCUSSION:
Page 16 Line 7: Low back pain can be abbreviated here.
FIGURES: Figure 2 & 3: I found the high, low, close terms confusing. Would there be any issue with using something like UCI (upper confidence interval), LCI (lower confidence interval), and aOR (adjusted odds ratio) to be related to the terminology used throughout the manuscript. I also believe the aOR should be presented on the top line not the bottom. Figure 4: There is a figure caption but the terms don't seem to be presented in the figure. Please add these to the figure, or remove the terms from the caption. If the terms are removed from the caption "Adjusted Odds ratio and 95% confidence intervals of the Association between Low back pain and Psychological distress (adjusted for sex, age socioeconomic status, and educational level)" should remain to explain the figure.

Underwood, Martin
Warwick University, Warwick Medical School REVIEW RETURNED 07-May-2021

GENERAL COMMENTS
At initial submission I made the following comment 'Clearly beyond scope of this paper but understanding if you ask the same question to people in Norway and Lithuania twice as many answer 'yes' in Lithuania, is really important. Is it something in the translation, the question having developed in English only, or is it a culturally driven difference in the interpretation of the question, or is there a real difference in prevalence? The authors may wish to comment on whether there may be reasons for their observations other than differences in prevalence. It might be interesting to see if global burden of disease data shows similar differences to shed some light on why this might be.' The authors have provided a very long description of the selection of measures for the study in response to referees. But they have not sought to address this point in the text. Some description of the lengths they went to address possibility of information bias and how confident they are that the differences observed are true differences.
I think in the limitations it should be stated that there was not a prespecified statistical analysis plan The updated figures do not appear to have been included in the resubmission

VERSION 2 -AUTHOR RESPONSE
Reviewer 2 I would like to thank the authors for taking the time to respond to my comments in detail. I have now reviewed these and they have been adequately implemented. How the exposures and Noted and appreciated.
outcomes were treated in the statistical models is now clearer. Outside of the responses, I have some minor comments that should be addressed. I apologize if I missed any of these in the original review.
Page 10 Line 1: Throughout the results, please present the 95% confidence intervals anytime a value from statistical models is reported to allow readers to easily determine the precision of the estimate. EG on line 19 "Whereas those with No formal education had a 44% increase in risk." The 95% CI should be presented with this Thank you for these comments.
All the data from models have now been presented with their associated 95% Confidence intervals.
Page 10 Line 10: The wording needs to be updated from 'risk' to 'odds' given the odds ratios were used for consistency. This also needs to be updated in subsequent paragraphs The word 'risk' has now been replaced with 'odds' Page 16 Line 7: Low back pain can be abbreviated here.
'Low back pain' has been abbreviated to 'LBP' Figure 2 & 3: I found the high, low, close terms confusing. Would there be any issue with using something like UCI (upper confidence interval), LCI (lower confidence interval), and aOR (adjusted odds ratio) to be related to the terminology used throughout the manuscript. I also believe the aOR should be presented on the top line not the bottom.
Apologies for this.
Our graphs were created in MS Excel and we are not able to alter the formatting and labelling of adjoining tables of this particular type of chart (high-low-close).
Figure 4: There is a figure caption but the terms don't seem to be presented in the figure. Please add these to the figure, or remove the terms from the caption. If the terms are removed from the caption "Adjusted Odds ratio and 95% confidence intervals of the Association between Low back pain and Psychological distress (adjusted for sex, age socioeconomic status, and educational level)" should remain to explain the figure.
Thank you.
The terms that did not appear in the chart have been removed.
Reviewer: 3 At initial submission I made the following comment 'Clearly beyond scope of this paper but understanding if you ask the same question to Thank you for these comments.
An explanation on some of the efforts to prevent such confusion has now been added to the text discussion section on page 14 Lines 6 -8. It reads thus: